This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A lipid membrane mimetic (Nanodisc) has been developed to study membrane proteins. Nanodiscs have been demonstrated to be valuable to study the cytochrome P450 monooxygenase family, with CYP3A4 being the most abundant in human liver. This particular member of the family metabolizes approximately 50% of commercial drugs. Our goal is to study many of the drug-like substrates that bind to CYP3A4 while incorporated into the natural environment of the lipid membrane. We wish to learn about binding affinities, stoichiometry, and localized conformational changes upon binding the drug targets utilizing our PLIMSTEX protocols.